Birth control pill for men could be five to ten years away

A first trial suggests the new oral contraceptive for men may be effective, but comes with side effects many women know all too well.

58 years after the birth control pill for women was approved for contraceptive use, a new oral contraceptive is being tested for men. A first trial with 100 men showed promising results: hormones that induce semen production sank to a level you would see in men who have been castrated. While on the drug, some of the men showed side effects similar to those women taking the birth control have endured for years, including weight gain and low libido. Despite these side effects, which stopped after the men went off the pill and their hormone levels returned to normal, many study participants said they’d take the pill in real life if it were available. We spoke with one of the researchers behind the trial, Arthi Thirumalai at the University of Washington, about why she’s hopeful we won’t have to wait another half century for a birth control pill for men.

ResearchGate: How does this male birth control pill work?

Arthi Thirumalai: The drug blocks the production of testosterone and sperm in the testicles. However, its active ingredient, dimethandrolone undecanoate (DMAU), binds to the androgen receptor more potently than testosterone, and is able to maintain male functions like libido, muscle mass, and mood despite the marked reduction in testosterone concentrations in the men taking the drug.

RG: How did you conduct this trial?

Thirumalai: 100 men were recruited, and 83 went on to complete the study. Nobody dropped out of the study for drug-related concerns or symptoms. Men received either placebo or DMAU (in either castor oil or powder in a capsule) in one of three different doses: 100 mg, 200 mg, or 400 mg. They were asked to take the pill daily in the morning, after eating a breakfast that contained 25-30 grams of fat for better absorption, for a total of 28 days.

On their first and last day of dosing, they were admitted to the inpatient unit for 24 hours and underwent hourly vital sign assessments and frequent blood sampling for measurement of drug levels and hormones. In between these two visits, they presented to our lab twice a week for assessment of vital signs, inquiry of any side effects or concerns or new medication use, drug accountability, and blood draw.

After the 28 days of drug exposure, they returned for visits to assess their recovery three and six weeks from last dose of drug. If their hormones and semen analysis were normal at six weeks out, they exited the study, otherwise they were followed until both of those were true.

RG: What were your results?

Thirumalai: Our study showed that DMAU at 200-400 mg dose, reversibly suppressed men's blood gonadotropins (FSH and LH) and testosterone concentrations to markedly low levels, akin to those you would see in men who have been castrated. Such low levels of these hormones, in prior contraceptive trials, have shown to translate into suppression of sperm production to levels consistent with effective contraception. At the same time, all men showed recovery of these hormones to normal even by three weeks from the last dose of the drug and had normal semen analyses when they exited the study. This study was too short to show sperm suppression as they only took the drug for 28 days, and the lifespan of sperm is 75 days. We also assessed mood and sex drive/sexual function with validated questionnaires, and these showed no differences between men receiving DMAU and those receiving placebo pills.

RG: What side effects did you see?

Thirumalai: The drug was well tolerated by the men. Despite such profoundly low testosterone concentrations, nobody complained of hot flashes, and only eight men on DMAU complained of a mild reduction in their libido, six of whom were in the highest dose group. Five men on DMAU complained of acne, but so did three men in placebo group. Men receiving DMAU gained 1.5-3.9 kg weight and had reduction in their HDL cholesterol by 7-17 mg/dL. Notably, there was no clinically relevant change in their liver enzymes, blood counts, prostate-specific antigen, or LDL cholesterol in this study. Their vital signs, including blood pressure and heart rate, also were not affected.

RG: How did the subjects respond? Would they take the drug in real life?

Thirumalai: Subjects responded well. Nobody dropped out due to side effects from the drug. We even administered a contraceptive acceptability questionnaire, and they did report that they would take the drug in real life if this were available. This is consistent with other previously published survey data among men across different countries, ethnicities, and socioeconomic groups.

RG: How far away are we from an oral contraceptive for men now?

Thirumalai: We are still a long way from showing that this drug works as an oral contraceptive for men. We need to study it in longer trials and first show sperm suppression and then test it in couples to show efficacy as a sole contraceptive agent. We also need to assess long-term safety of the drug. However, these early results are promising for this novel agent. If everything goes well, we could be looking at a drug in five to ten years.

RG: What is the next step for your drug?

Thirumalai: We are starting a three-month trial of this drug with and without the combination of a progestin (Levonorgestrel) in April 2018.

RG: Have you spoken about your research with male friends or family members? What do they think about the pill?

Thirumalai: Yes, we have discussed this with our families and friends. There is a lot of excitement and interest on everyone's part with the idea of expanding options that can be available for men to choose from for taking control of their fertility. A pill is easier in some ways in that it is oral, so they can take it themselves and don't need to go to a medical provider. Obviously, they want to know about side effects and the fact that there weren't that many to note from this study was encouraging to them. They are eager to see the results of future studies.

 

Image: Beria Lam Wikipedia Commons